Inhaled KMUP-1 Prevents Allergic Pulmonary Vascular Inflammation and Remodeling via NO and Suppressed MMP-9 and ICAM-1/VCAM-1

Liu, Chung-Pin; Hsieh, Chung-Han; Wu, Bin–Nan; Yeh, Jwu‐Lai; Dai, Zen‐Kong; Chai, Chee‐Yin; Chen, Ing‐Jun

doi:10.2174/187152812800958960

Cited by 7 publications

(2 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, effective protection of endothelial cells is essential for the prevention and treatment of cardiovascular injuries. Our previous studies have shown that KMUP‐1 can exert beneficial effects on various diseases associated with vascular dysfunction . In addition, KMUP‐1 was shown to have protective effects against the hypoxia‐induced injury in pulmonary artery and hepatic tissues.…”

Section: Discussionmentioning

confidence: 98%

Activation of endothelial NO synthase by a xanthine derivative ameliorates hypoxia-induced apoptosis in endothelial progenitor cells

Hsu

Dai

et al. 2016

Journal of Pharmacy and Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 98%

Activation of endothelial NO synthase by a xanthine derivative ameliorates hypoxia-induced apoptosis in endothelial progenitor cells

Hsu

Dai

et al. 2016

Journal of Pharmacy and Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Numerous authors claim that high levels of MMP-9 may destroy ECM in airway mucosa. This damage could stimulate chaotic tissue regeneration, which may result in increased fibrosis and, thus, it would determine a detrimental effect of MMP-9 on disease progression [ 49 , 50 ]. The enthusiasts of the opposite concept suggest that MMP-9 may digest improperly deposited ECM components, and thus it actually might play a protective role against tissue fibrosis and airway remodeling [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Inhaled corticosteroids do not reduce initial high activity of matrix metalloproteinase (MMP)-9 in exhaled breath condensates of children with asthma exacerbation: a proof of concept study

Grzela

Zagórska

Krejner

et al. 2016

cejoi

View full text Add to dashboard Cite

Inhaled corticosteroids (ICS) are the key component of asthma treatment. However, it is unclear whether they could control the activity and level of matrix metalloproteinase (MMP)-9, which is an important factor in asthma-associated inflammation and airway remodeling. Therefore, the aim of this proof of concept study was to analyze the influence of increased doses of ICS on MMP-9 in exhaled breath condensates (EBC) of patients with allergic asthma exacerbation. Apart from MMP-9, the assessment concerned selected inflammation markers – exhaled nitric oxide (eNO) and cytokines (IL-8 and TNF).The study involved a small group (n = 4) of individuals with asthma exacerbation. The intervention concerned increased doses of ICS with β-mimetics for 4 weeks. In addition to clinical evaluation, eNO measurements and EBC collections were done before and after 4 weeks of intense ICS treatment. The biochemical assessment of EBC concerned MMP-9, IL-8 and TNF. The data were compared to results of healthy controls (n = 6).The initial levels of eNO, MMP-9 and TNF in EBC were higher in the asthma group than in controls. In all subjects IL-8 levels were below the detection limit. After 4 weeks of ICS treatment in all patients we observed improvement of clinical and laboratory parameters. Interestingly, despite reduction of eNO and TNF, the activity of MMP-9/EBC remained on the initial level.Practical relevance of our results is limited by a small group. Nevertheless, our data suggest that ICS, although sufficient to control symptoms and inflammatory markers, may be ineffective to reduce MMP-9/EBC activity in asthma exacerbation and, possibly, airway remodeling.

show abstract

Buffered l‐ascorbic acid, alone or bound to KMUP‐1 or sildenafil, reduces vascular endothelium growth factor and restores endothelium nitric oxide synthase in hypoxic pulmonary artery

Kao

et al. 2015

The Kaohsiung J of Med Scie

View full text Add to dashboard Cite

Ascorbic acid bound to KMUP-1 and sildenafil were examined for their antioxidant effects on vascular endothelium growth factor (VEGF) and endothelium nitric oxide synthase (eNOS) in hypoxic pulmonary artery (PA). Inhaled KMUP-1 and oral sildenafil released NO from eNOS. The effect of buffered l-ascorbic acid, alone and bound to KMUP-1 or sildenafil, for treating pulmonary arterial hypertension (PAH) is unclear. In this study, the antioxidant capacity of ascorbic acid increased the beneficial effects of KMUP-1 on PAH. KMUP-1A and sildenafil-A (5 mg/kg/d) were administered to hypoxic PAH rats. Pulmonary artery blood pressure, and VEGF, Rho kinase II (ROCK II), eNOS, soluble guanylate cyclase (sGC-α), and protein kinase G expression in lung tissues were measured to link PAH and right ventricular hypertrophy. Hypoxic rats had higher pulmonary artery blood pressure, greater PA medial wall thickness and cardiac weight, and a higher right ventricle/left ventricle + septum [RV/(LV+S)] ratio than normoxic rats. Oral KMUP-1A or sildenafil-A for 21 days in hypoxia prevented the rarefaction of eNOS in immunohistochemistry (IHC), reduced the IHC of VEGF in PAs, restored eNOS/protein kinase G/phosphodiesterase 5A; unaffected sGC-α and inactivated ROCK II expression were also found in lung tissues. In normoxic PA, KMUP-1A/Y27632 (10μM) increased eNOS and reduced ROCK II. ROCK II/reactive oxidative species was increased and eNOS was reduced after long-term hypoxia for 21 days. KMUP-1A or Y27632 blunted ROCK II in short-term hypoxic PA at 24 hours. l-Ascorbic acid + l-sodium ascorbate (40, 80μM) buffer alone directly inhibited the IHC of VEGF in hypoxic PA. Finally, KMUP-1A or sildenafil-A reduced PAH and associated right ventricular hypertrophy.

show abstract

Inhaled KMUP-1 Prevents Allergic Pulmonary Vascular Inflammation and Remodeling via NO and Suppressed MMP-9 and ICAM-1/VCAM-1

Abstract: Inhaled KMUP-1, preventing allergic pulmonary vascular inflammation and remodeling, would be useful for the treatment of asthma and respiratory obstruction disease.

Cited by 7 publications

References 36 publications

Activation of endothelial NO synthase by a xanthine derivative ameliorates hypoxia-induced apoptosis in endothelial progenitor cells

Activation of endothelial NO synthase by a xanthine derivative ameliorates hypoxia-induced apoptosis in endothelial progenitor cells

Inhaled corticosteroids do not reduce initial high activity of matrix metalloproteinase (MMP)-9 in exhaled breath condensates of children with asthma exacerbation: a proof of concept study

Buffered l‐ascorbic acid, alone or bound to KMUP‐1 or sildenafil, reduces vascular endothelium growth factor and restores endothelium nitric oxide synthase in hypoxic pulmonary artery

Contact Info

Product

Resources

About